Side-by-side · Research reference

ARA 290vsRetatrutide

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 2HUMAN-REVIEWED17/59 cited

BPhase 2HUMAN-REVIEWED10/41 cited

ARA 290

EPO-Derived Peptide · Innate Repair Receptor Agonist

4 mgDaily doseBrines 2015 Culver 2017

28 daysPhase 2 durationCulver 2017

Non-erythropoieticSafety profileBrines 2015 Liu 2014

SQ · DailyBrines 2015 Culver 2017

Retatrutide

Triple-receptor agonist · Phase 3

1–12 mgWeekly doseJastreboff 2023

24.2%Body-weight ↓Jastreboff 2023

~6 daysHalf-life (est)

SQ · Abdomen · Once weekly

01Mechanism of Action

Parameter

ARA 290

Retatrutide

Primary target

Innate repair receptor (EPO receptor / CD131 heterodimer)

GLP-1R + GIPR + Glucagon receptor (triple agonism)Jastreboff 2023

Pathway

EPO/CD131 → JAK2 activation → PI3K/AKT, MAPK signaling → anti-inflammatory, anti-apoptotic cascades

Triple-receptor activation → ↑insulin (GLP-1+GIP), ↓gastric emptying, ↑lipid handling, ↑energy expenditure (glucagon component)Jastreboff 2023

Downstream effect

Tissue protection, nerve fiber regeneration, suppression of inflammatory macrophage activation, altered T-cell differentiation (↑Treg, ↑Th2, ↓Th1)Liu 2014 Culver 2017

Maximal weight loss across class. Glucagon component drives lipolysis and energy expenditure beyond GLP-1+GIP aloneJastreboff 2023

Feedback intact?

N/A — does not interact with hematopoietic EPO receptorLiu 2014

—

Origin

11-amino-acid sequence from EPO helix B, engineered to eliminate hematopoietic activity while retaining tissue-protective properties

Synthetic peptide engineered for balanced affinity at three incretin / glucagon receptorsJastreboff 2023

Antibody development

Not reported in clinical trials

—

02Dosage Protocols

Parameter

ARA 290

Retatrutide

Standard dose (Phase 2)

4 mg / dayBrines 2015 Culver 2017

Sarcoidosis SFN and diabetic neuropathy trials.

—

Frequency

Once daily

Self-administered subcutaneously.

Once weekly

Duration

28 days (Phase 2)Culver 2017

Corneal nerve improvements observed by day 28.

Indefinite for chronic indication (presumed)

Evidence basis

Phase 2 RCTsCulver 2017 Brines 2015

64-subject sarcoidosis trial, type 2 diabetes trial.

Phase 2 trial; Phase 3 ongoingJastreboff 2023

Route

SubcutaneousBrines 2015

—

Timing

Any time of day

No circadian dependence reported.

Any time of day

Standard dose

—

12 mg / week (max efficacy)Jastreboff 2023

Phase 2 trial dose. Phase 3 dosing TBD.

Titration schedule

—

2 mg → 4 mg → 8 mg → 12 mg over 16 weeks

Reconstitution

—

Investigational; not commercially available

Half-life

—

~6 days (estimated from class)

03Metabolic / Fat Loss Evidence

Parameter

ARA 290

Retatrutide

Primary effect

Improved metabolic control (HbA1c, fasting glucose)Brines 2015

Secondary to neuropathy treatment; direct lipolytic effects not established.

—

HbA1c

Significant reduction vs placebo

Observed in type 2 diabetes + neuropathy trial.

—

Fasting glucose

Improved in ARA 290 group

—

Body composition

Not directly quantified

Fat loss not a primary endpoint; metabolic improvements may reflect insulin sensitivity.

—

04Side Effects & Safety

Parameter

ARA 290

Retatrutide

Injection site reaction

Mild, transient

—

Hematopoiesis

None — non-erythropoietic

Distinguishes ARA 290 from native EPO.

—

Cardiovascular

No thrombotic events or hypertension reported

—

Immunogenicity

No antibody formation reported

—

Tolerability

Well-tolerated in Phase 2 trialsCulver 2017 Brines 2015

—

GI symptoms

—

Nausea, vomiting, diarrhea (very common, dose-dependent)Jastreboff 2023

Heart rate

—

↑ resting HR (3–7 bpm at 12 mg)Jastreboff 2023

Glucose handling

—

Glycemic improvement; rare hyperglycemia from glucagon component

Pancreatitis risk

—

Class warning

Thyroid C-cell tumours

—

Class warning (presumed)

Pregnancy / OB

—

Avoid (insufficient data)

Absolute Contraindications

ARA 290

·Hypersensitivity to ARA 290

Retatrutide

·MTC personal or family history (presumed class effect)
·Pregnancy / breastfeeding

Relative Contraindications

ARA 290

·Active malignancy (theoretical EPO-axis concern; not observed in trials)

Retatrutide

·Severe gastroparesis
·History of pancreatitis
·Severe cardiovascular disease (HR signal)

05Administration Protocol

Parameter

ARA 290

Retatrutide

1. Preparation

Reconstitute lyophilised powder per manufacturer instructions. Use sterile technique.

Investigational peptide. Research vials reconstituted with bacteriostatic water per label.

2. Injection site

Subcutaneous — abdomen, thigh, or upper arm. Rotate sites to avoid lipohypertrophy.

SQ — abdomen, thigh, or upper arm. Rotate weekly.

3. Timing

Once daily, any time of day. Self-administered in Phase 2 trials.Brines 2015

Once weekly, same day.

4. Dosing

4 mg daily for 28 days (Phase 2 protocol). Duration for chronic use not established.Culver 2017

Refrigerate 2–8 °C. Light-protected.

5. Storage

Lyophilised: store at controlled room temperature. Reconstituted: refrigerate, use within specified timeframe.

27–31G, 4–8 mm insulin syringe.

06Stack Synergy

ARA 290

+ BPC-157

Moderate

View BPC-157 →

ARA 290 targets the innate repair receptor (EPO/CD131) for nerve regeneration and anti-inflammatory signaling, while BPC-157 promotes angiogenesis and tissue repair through distinct mechanisms (likely involving VEGF, growth hormone receptor pathways). Combined, they may address both neuroinflammation and structural tissue repair in neuropathy or injury models. No direct clinical data; mechanistic overlap in tissue protection.

ARA 290: 4 mg SQ · daily
BPC-157: 250–500 mcg SQ · daily
Frequency: Once daily, same or separate injections
Primary benefit: Nerve regeneration, pain reduction, tissue healing

Retatrutide

— no documented stacks